Though Down syndrome affects people around the globe, money to research the condition lags far behind that of breast cancer or autism. Despite advancements in rights and opportunities for people with disabilities, families of children with Down syndrome continue to battle against diminished expectations.
Thanks in no small part to the efforts of the Global Down Syndrome Foundation and the Linda Crnic Institute, a new age of understanding has begun. These Denver-based organizations seek to reframe the perception of Down syndrome through innovative research.
ABILITY’s Chet Cooper met with the executive director of the Linda Crnic Institute, Edward McCabe, MD, and members of including program coordinator Dee Daniels, RN; director of education Patricia McVay, MS; assistant professor Kristin Jensen, MD; and Sie Center medical director Fran Hickey, MD, to discuss the road ahead.
Chet Cooper: How did you become a part of the clinic?
Edward McCabe: I had been chair of pediatrics at UCLA for 16 years, but I came here in August 2010 because I was attracted to the mission of eradicating the medical and cognitive effects of Down syndrome. It’s a very different condition than it was 30 years ago. By changing the educational culture, and by providing early intervention, we’ve enhanced people’s lives
Patricia C. Winders, a physical therapist who literally wrote the book on gross motor skills for people with Down syndrome, had been at the clinic by herself for two and a half years before we began adding more people. Today we’re up to about seven faculty and eight staff members. Even with only 15 people onboard, we stand as the largest organization devoted to Down syndrome in the United States and possibly in the world.
We’re also unique in that we perform not only foundational research in the biology around Down syndrome, but also translational, clinical and outcomes research. We perform some clinical trials and offer health services in our clinic.
Cooper: Let’s talk about the trials you’re working on.
McCabe: Adults with Down syndrome face early onset Alzheimer’s disease, so we believe there should be clinical trials of these adults with any drug that’s been approved for Alzheimer’s by the Food and Drug Administration. We already know that physical activity improves quality of life and cognition, so we’re looking into a study of exercise right now.
Cooper: How would such a study work?
McCabe: We would probably contrast an exercise group against a sedentary group and observe change over a set time period. We’ve also been approached by a pharmaceutical group that wants us to educate them about leukemia that is associated with Down syndrome.
Cooper: What other conditions are typically associated with Down?
Fran Hickey: The co-morbidity that gets the most press is heart disease, which affects about 40 percent to 50 percent of the kids, and 20 percent to 25 percent of them very seriously. These children develop a thing called a canal, which is an abnormal interaction between the atrium and the ventricles. Fortunately the outcome for that defect has greatly improved over the last 10 or 15 years. Now there is better intervention, better surgeries and better anesthesia.
McCabe: And people with Down syndrome also have improved access to care today. As recently as 1990, the medical profession said: We’re not going to give people with Down syndrome the life-saving surgeries they need. That has changed.
If 20 percent to 25 percent of a group is dying between the ages of two and four, that obviously has a huge impact on overall life expectancy. Life expectancy began to change around the year 1990, because of access to these surgeries.
Hickey: We’re trying to get data on why, exactly, things have improved. It mostly has to do with treatment of cardiac conditions; in some instances, we can patch patients with stents, so we don’t have to open their chests. Some of the other defects are not that hard to treat, and some conditions naturally go away on their own. Those are probably the biggest changes.
There is a lot of research associated with Down syndrome that can help everybody. Who isn’t concerned about Alzheimer’s? Everybody knows somebody with it. But about 50 percent of people with Down syndrome get it, and it starts earlier. That’s a big concern.
About a quarter of people with Down syndrome have small ear canals—smaller everything, in fact—so they experience a lot of conductive problems when they’re younger. Sensory neural problems, such as deafness, have significantly decreased. Years ago, it was estimated that 20 percent of people with Down syndrome were deaf at birth. Today that’s 1 percent to 2 percent, at most.
Dee Daniels: That’s because conditions are now identified earlier.
Hickey: Down syndrome research has allowed all people to improve, because it’s created technology that helps everybody. Research on facial and ear anomalies that has benefited people with Down syndrome has benefited other kids with those challenges as well.
An inability to hear affects your development from the start. A lot of people with Down syndrome have an eye-movement disorder called strabismus. As a result, their risk of developing cataracts is higher than it is for the rest of us, so their eyes have to be watched closely. They also tend to have more problems with breathing and eating, because everything’s smaller.
We know that difficulties with the chest often cause death in kids with Down syndrome, because those with the most severe problems end up aspirating. Every child patient of mine who has passed away has had problems with the lungs. We need some clinical studies to look into this. Fran’s work in this area has really energized the medical community.
McCabe: I bumped into one of our colleagues yesterday, and he began telling me how excited he was to have access to some mouse-lung models of Down syndrome.
Cooper: What do mice have to do with understanding the condition?
McCabe: The mouse has the chromosome 21, which is also found in humans. My colleague has a mouse that’s trisomic—meaning that it has three chromosomes instead of the usual two. It has a bit of chromosome No. 10, a bit of chromosome No. 16, and a bit of chromosome No. 17, so this mouse is allowing the team to notice some striking differences. Now it’s just a question of breaking the code. Fran is talking to clinical sub-specialists and getting them to make the connection between seizures and Down syndrome, or between autism and Down syndrome.
Hickey: We had a pretty good study in Cincinnati that looked at the percentages of children with Down syndrome and autism, both of which my son has. He kind of went downhill when he was about five or six, and then he stabilized. My wife was phenomenal through the whole experience. My son has made some progress, and spending time with him is the highlight of my day.
Close to 5 percent or 6 percent of kids are likely to have a dual diagnosis of Down syndrome and autism. The incidences of kids who solely get autism is close to 1 percent now—1 out of 110 in the latest data.
Cooper: And for boys the numbers are 1 out of 70.
Daniels: Some kids are misidentified as being autistic, when in fact their condition is really an expressive speech disorder. They just haven’t had enough aggressive early intervention.
Hickey: This is the thing: I’m not looking for the Holy Grail for my kids. I’m looking to maximize what they can do. They can exercise, for example. There are people who are 30 to 40 years old and who have never had any exercise. They’ve never had a chance to do anything. Exercise makes people’s lives better. It can affect the incidence of Alzheimer’s. It can affect a lot of things.
Cooper: Have you thought about tying the exercise study into the Special Olympics?
McCabe: The Centers for Disease Control [CDC] is doing a study of Special Olympics International and, overall, they’re very concerned about the health of the athletes. That’s where Kristin Jensen comes in. She’s here, and she’s trained in both internal medicine and pediatrics. She’s well prepared to research those health outcomes as well. That’s one of the areas we talk to her about. There’s a whole group of folks at the CDC who deal with quality of life issues.
Hickey: Quality of life is an area that parents really want to know about. They want to know how their kids can be happy. As a physician, you always think you’ve got to give them all the facts and information, but you can give it to them in different ways.
McCabe: Yeah, families tend to hate genetic counseling for that very reason. If you hear the horror stories that we’ve heard, you understand why. For instance, I know of a case of a family with a three-month-old daughter who had mosaic trisomy 21, a form of Down syndrome where not all the cells are affected. The parents asked, “How do we know the percentage of mosaicism in the blood, brain and other organs of our child?”
The genetic counselor said, “I guess you’ll have to wait for an autopsy.”
McCabe: In cases of mosaic Down syndrome, the affected cells determine how mild or severe the condition will be. In effect, a person could have, for example, legs or arms that are Down syndrome in nature, while the rest of the body remains free of the extra chromosome.
Cooper: Can the condition be inherited? Can a person have genetic disposition toward it?
McCabe: Yes, but all parents really want to know is this: What is my child going to be able to do when they grow up? And so that’s what we talk about. Let’s say your child has Down syndrome and there’s no expectation that he’s going to be able to graduate high school, go on to community college, or get a job. When the kid is in third grade and doesn’t want to do his homework, you might figure, Why get into a big fight? What difference does it make?
Daniels: Parents are often taught not to expect much. One of the mothers in our clinic came in when her child was two or three, and we said, “Why haven’t you started speech therapy yet?” As it turned out, the school where the child was enrolled told the mother that, since her child wasn’t yet speaking, there was no reason to start speech therapy.
But perhaps they could have explored the possibility that the child was not speaking yet because of a lack of speech therapy. We’ve kind of raised the bar in our clinic, in respect to what families should try to expect. We put in place the services to support those goals.
McCabe: If a woman happens to be pregnant and her fetus is identified as being at risk for Down syndrome, we would like to be sure that the information she receives enables her and her partner to make a decision about the child that is absolutely accurate. We want to make sure that it includes information about the potential, and the quality of life, that individuals with Down syndrome can achieve, not just negative medical information.
Cooper: Many parents no doubt feel the birth of their child is the best thing that’s happened in their lives, even with the health complications it might entail. Have you considered a “train-the-trainer” component to your clinic?
McCabe: I told a genetic counselor who recently started with us that our job is to reinvent genetic consulting for Down syndrome, so that people are willing to come in for it. The letter we send to families is much longer than is typical, because we go into quality-of-life concerns.
I tell parents, “Get out your red pen, go through our letter and tell us what you like and don’t like, because you’ll help us communicate better in the future.” The counselors trained here go out and populate all obstetrician offices everywhere, so communication is important.
Cooper: What does a genetic counselor do?
McCabe: Genetic counselors talk to family members about why their child has Down syndrome. In some of the families we’ve seen, the fathers experience serious guilt that, somehow, they’ve done something in the past that caused Down syndrome in their children.
A lot of what we do in genetic counseling is say, “Down syndrome is just something that statistically happens in nature. It’s random. Nobody caused it. There’s nothing you could have done, nothing you could have prevented, and nothing you did that caused this.”
Cooper: One of the people who works with us, a single mother, adopted two young kids with different disabilities. One of them has Down syndrome, and when she adopted him, she was told that he would never speak, so she taught him sign language. Now he speaks and signs!
Hickey: To this day I bang my head against the wall in disbelief that people aren’t teaching their kids to sign. If you teach them sign language, they’ll really take off once the verbal stuff kicks in.
Daniels: We used to say, “Don’t teach them sign language, because then they’ll rely on signing.”
Hickey: That was probably the worst advice ever given, and it comes from grandparents all the time.
McCabe: We want to develop best practices that get adopted, so that a child who’s seeing a general practitioner in the middle of nowhere has access to information that he just doesn’t have access to now.
Cooper: I wouldn’t wait for best practices. Put something out there that says, “Pretty good practices.”
Hickey: (laughs) That’s the same thing the head of best practices told me. A lot of people might say: There’s nothing out there for people with Down syndrome. But we’ve got to find it. Progress, historically, has been driven by parents and family groups. One of the reasons I came here was to try to make a huge change. We’d done that in Cincinnati, because the physicians were at the top level of knowledge, and people were doing the right thing.
But you can go all the way from here, in Denver, to California and find there’s hardly any support for families dealing with Down syndrome. A lot of people get their medical information off of websites.
Daniels: We get a lot of calls from rural physicians around here, asking for guidance. We’ve done a lot of outreach, too.
Patricia McVay: The reason I joined this team is because I know of no other place in the country where the educational paradigm and the medical paradigm are coming together.
Cooper: I’ve been around this for a while, and I haven’t heard of anything.
McVay: There may be teaching hospitals that are educating kids, but nobody else brings a whole team into play for a family. I tell parents that I’m an educator and I’ve been a school principal, so that they know where I’m coming from. Then the parents are asking, “Oh, you’re going to help us with school? Will you talk to the teachers, the principals, and help us with the Individualized Educational Programs [IEP], too?” They get excited.
McCabe: This is my second time at the University of Colorado. I was here from ’76 to ’86, as a fellow and as junior faculty, and I started the Metabolic Disease Clinic here at the time. This state is a microcosm for the United States. You really get a feel for the impact you’re having. If we can figure out what to do here, we can begin to take that information to Kansas, to Nebraska, to Wyoming—anywhere, really.
There are 300 to 500 genes on chromosome 21, and we don’t know what a lot of them do, so that’s what people are studying. We’re trying to understand the relationship between the third copy of this chromosome, for example, and the genes responsible for midface hypoplasia, for heart disease, for all of these co-morbidities. We’re undertaking a study to look at the protein biomarkers in blood.
We especially want to look at congenital heart disease, because by the time a woman who’s having a child with Down syndrome knows she’s pregnant, the congenital heart disease is already there. There’s really nothing she can do about it. But if we can find proteins that are associated with the congenital heart disease, potential drug treatments become available.
Daniels: This is a multidisciplinary clinic, so we have multiple people seeing patients when they come in. I gather the patient’s medical records before the visit and create a summary for everybody who’s seeing that patient, so we sort of know who he or she is beforehand. Dr. Hickey and I see the patient for medical issues, we have a speech therapist here, and we have our physical therapist, Pat Winders.
We also have a feeding therapist, because we know many of our children have uncoordinated suck or feeding issues, especially given their facial structures. And we have a social worker who helps families find resources in the community to help them process the diagnosis and their feelings about it.
Often, we’ll help families coming in from rural places to get gas cards and find lodging. We recently hired an educational coordinator, who comes in and talks to our children about their school experiences and who looks at their IEPs to make recommendations. She’s even going out into the community to meet with school administrators to talk with them about inclusion and things like that.
Cooper: What’s the age range of the patients you service?
Daniels: Zero to 21, right now. Dr. Jensen, whom we recently hired, deals with pediatrics and adults, so eventually we hope to have services for older children or an adult clinic, down the line. We have point people in all of the specialties: pulmonologists, immunologists, allergists, cardiac physicians. We’re doing some studies with autoimmune conditions, too, so we’re working with dermatologists and gastroenterologists for studies of celiac disease, an allergy to wheat. There’s a lot of networking going on here. Everybody’s excited about all the research opportunities that can come out of the clinic.
McCabe: So much focus is on the kids, and when you get past that 21- or 22-year-old time horizon, you kind of disappear. But with Kristin here, we’ll be able to help develop and then study a transition program. We plan to optimize it as a model for other centers, so that patients don’t disappear from the system when they become adults.
Cooper: Will you also be looking at employment prospects?
McCabe: We have the Search program, which is a school-to-work transition program. Our intern, Genesis, is a young woman who has an intellectual developmental disability. We’ve had her here for about three months, and we’re expanding her duties to include general office work.
One thing I can assure you: If you don’t stimulate kids, they won’t do as well. We know the outcome when we warehouse and institutionalize people. We don’t yet know the outcome, however, if we optimize. One child we know just started kindergarten. He reads at a fifth-grade level. We have to work on his fine motor skills, yes, but if he hadn’t been read to or challenged—if the expectations for him had not been high—he wouldn’t be where he is now
McVay: Schools have to remove the labels, take away all of the typical things they associate with Down syndrome and go, “There are no limits. There are no boundaries. Let’s look at these young people as we would other students.”
At a postsecondary school for kids who were 18 to 21, I could tell which students had been included throughout their school careers and which had been segregated. The difference in their abilities to communicate, socialize or navigate the world was huge. The kids who had been included were so much more successful as they moved into jobs and into society.
Once you place a kid with his peers, most predictions are found to be wrong. So we really have to work with special-education folks in changing their thinking about the ability of these kids.
Kristin Jensen: As a physician, I’ve seen people with Down syndrome get out into the adult world and run up against the fact that many providers don’t quite know how to reconcile the fact that a person has Down syndrome with the fact that she’s 35, or he’s 65.
My research goal, ultimately, is to start figuring out how we can improve the transitions, and look at actual improvement in health outcomes, as opposed to just moving a person from this office to a different one. My big interest is in that transition period and how it can be improved.
I would like to also create a baseline of care for the adult patient. How do we make sure he’s receiving the appropriate screenings as a person with Down syndrome? I grew up with an uncle who had Down syndrome, and it boggled my mind that his physicians had no idea how to handle the fact that he was 60-odd years old and at the same time giggly and wanting to tell jokes and limericks all the time.
We have to deal with both sides of the picture. And it’s not that hard, but if you haven’t been exposed to it and you haven’t been given any inclination of how to approach those patients, there’s a huge amount of anxiety. We need to decrease those barriers. It’s not rocket science. We just have to do it.
McVay: Yesterday I was at the Coleman Institute conference on cognitive disability, and I met a parent whose son is 35 with Down syndrome. The parent said, “I don’t understand why you’re still having to do inclusive practices; I fought for that when my son was little!”
That’s a really common assumption: We’ve already fought the fight; it’s all done. I said to this woman, “Please know that your fight was good. It paved the way, but the sand has fallen back in the hole, and the way isn’t clear anymore, so we have to do it again.”
McCabe: I think it’s important to recognize that each person with Down syndrome is a unique individual with special talents. The job of educators and family and everyone who comes in contact with that person is to make sure he is able to reach his potential in each of the areas in which he has talents. In that way, he proves himself to be just like every other child. No parents want their children to have labels.
We hear so often: “Oh, that’s just Down syndrome. Everyone with it looks the same.” But a study determined that, in fact, they look more like their siblings than they do other kids with Down syndrome. Genetically, they’re more like everybody else than they are different. We have to recognize that. Chromosome 21 is the smallest of the 44 chromosomes. There’s just that puny little Y chromosome that sneaks in and causes all the trouble. (laughter)
Cooper: Is there any research on cognitive issues and the relevant chromosomes?
McCabe: There are duplications and deletions. The variation in cognition among people with Down syndrome is so large that I’ve actually started listing it as a co-morbidity. Because I think, again, to say all children and adults with Down syndrome have similar cognitive abilities is an overgeneralization. We don’t really know what causes that wide a spectrum, but it’s one of the things we’re interested in.
I think we need to think beyond chromosome 21, because there may be other chromosomes or genes that may be involved, as well as varying experiences both in utero and after a child is born. As we talk about educational attainment, we can’t forget that we’re a product of our environment as much as we are a product of our genetic background. We need to understand how the environment actually modifies us.
Cooper: Can you give me an example of a modification?
McCabe: There’s a classic example in the fetal origins of adult disease. It came out of what’s called the Dutch Hunger Winter studies. The backstory is this: In the last year of World War II, the Dutch were going to revolt against the Nazis, and the Nazis got upset. So from October to November of that last winter of the war—one of the coldest winters in history—the Nazis cut off supplies of gas and food. In response, the Dutch got their food to market through canals. But the canals froze, so the Dutch could no longer get food from the eastern, agrarian part of the country to the western metropolitan areas.
The Dutch severely reduced their caloric intake, and some even starved. As Europeans do, they kept good records of these things. They realized that if a fetus were in utero during the Dutch hunger winter, that baby was born small. But as food became available after World War II, those people who had been born underweight became obese, got hypertension, high blood pressure, and developed type 2 diabetes and coronary artery disease.
Lamb farmers have known this for centuries: The way you get big lambs that go to market is to starve the ewe and, once the lamb is born, feed the lamb as much as it will eat.
Cooper: Do you think that there’s some correlation between that discovery and mothers who have children with Down syndrome?
McCabe: We don’t know. We do know there’s one hypothesis that autism and schizophrenia may be a result of the mother undergoing extreme anxiety while the fetus is in utero. We are developing scientific tools now to look at these chemical modifications and understand them.
Cooper: People talk about the distinction between nurture and nature, but this seems all about nature, doesn’t it?
McCabe: Right. I founded and am co-director of the Center for Society and Genetics at UCLA, and we argued that the whole nature/nurture controversy is contrived, that it’s all one, and you can’t separate it.
The egg that became you was developing inside your mother while she was in utero inside your grandmother. It’s really all about multigenerational effects. I know my mother’s situation when she was pregnant with me, but I have no idea of what my grandmother’s situation was when she was pregnant with my mother.
We used to teach this stuff at UCLA. The eggs are all developed before a woman is born, and then they’re just suspended, ready for a sperm to come along. Your grandmother’s grandmother was developed when her mother was in her mother, so it’s very possible to get a multigenerational effect if there’s epigenetics going on.
Cooper: How might physical therapy be beneficial for people with Down syndrome?
Winders: For children with Down syndrome, the resting tension of the muscle is much less than it is for you. It’s floppy. A typical child will feel firm when you pick him up, but a child with Down syndrome will not. When you reach down to touch your toes, you probably don’t get down there real easily. But the hamstrings of a person with Down syndrome are nice and loose.
So these are just some of the differences, and they’re particularly evident in the ankles. That’s where you really see a difference, because that extra stretch and flexibility in the ankles makes people with Down syndrome walk with a more flat-footed posture. Physical therapy takes into consideration what those physical problems are, such as the fact that people with Down syndrome have hypotonia—or lax ligaments—and it tries to help them develop strong bodies with good posture and alignment, which is a foundation for exercise later in life.
When I see babies, I think about how I want them to be as adults, so I’m building in the posture and the walking pattern and the strength that they can continue to develop over time. We might work on specific skills in the birth-to-walking period, but what we’re really doing is giving these kids the right foundation for when they become adults.
Cooper: How do you successfully lay that foundation?
Winders: I’m aggressive about knowing the critical time for interventions. I used to joke with a speech therapist friend of mine that her critical period was from birth to death. I want all children to do community programs or just go to the playground. I want them to be in soccer and dance or gymnastics or whatever they’re interested in. That way, they’ll further refine their body and their movements through the things they’re interested in. I see most kids in the period from birth to walking, and then I see them for the next two to three years. After that, I see them periodically to make sure they learn to ride a tricycle and run. I want to make sure they’ve refined their walking pattern.
I focus on what I want to help these families develop, and I have strategies to make sure I’m only making the family come for a physical therapy appointment when it’s most important for them. They shouldn’t have to make it a way of life.
Some parents have said they feel like they’re just a taxi, taking their kids from appointment to appointment. So my model is parent training. That way the parent and child get to practice things together in a way that works.
McCabe: But they do love coming in to see you. Families leave your room laughing and grinning. It’s great.
Winders: You want it to be a fun, successful experience for everybody. The last thing any of us wants to do is spend hours on things that frustrate us because we’re not good at them. What we’d all rather do is work on things we’re interested in and gradually approach the things that are more challenging.
Cooper: Are you doing any work with the National Institutes of Health?
McCabe: I went to the head of the Eunice Kennedy Shriver National Institute of Child Health and Human Development [NICHD], where the director, Alan Guttmacher, has a new attitude about funding research to improve the quality of life for people with Down syndrome. We came up with 15 institutes, in addition to NICHD, who have funding for conditions that relate to Down syndrome. So now NICHD has asked me to make a presentation and point out ways we can increase funding by approaching all 16 institutes. If we could get funding from all of them, we could dramatically increase funding for Down syndrome research.
Cooper: Has the number of Down syndrome cases increased as women wait longer to have children?
McCabe: While there is a higher probability, per pregnancy, as the maternal age increases, the vast majority of fertility is in younger women. So younger women, overall, have more babies with Down syndrome.
Hickey: The termination rate for women pregnant with babies that have been identified as having Down syndrome is high in Northern Europe, where people have ready access to abortion. While it was predicted 5 or 10 years ago that the number of Down syndrome cases in those places would decrease because people are terminating more, it is actually staying the same.
A research study in Connecticut indicated the termination rate of people with Down syndrome has gone up in the United States. But as mothers get older, a lot of them theoretically have one kid or none. So a lot of them end up keeping the kids. It’s important to be able to maximize what these kids can do.
Cooper: Are the numbers increasing, or is data collection improving?
McCabe: The numbers are going up. The population of the United States is increasing, pretty much linearly, and the population of people in the United States with Down syndrome is actually increasing at a faster rate.
Hickey: People with the condition aren’t dying as young as they used to, either, so it’s a double-edged sword.
McCabe: The life expectancy for a baby born with Down syndrome is 60 years, yet we know of a mother who was told in 2003 that her baby’s life expectancy was three years of age. Why put that kind of information out, unless you want to coerce people into termination?
Someone at the International Congress of Human Genetics told me obstetricians consider a fetus with Down syndrome the same way they think of a uterine tumor! We presented our materials about coercion and eugenics at the American College of Medical Genetics meeting last spring, and a lot of people came up to us and said it’s about time that people actually talked about this stuff. This sort of awareness, this education, needs to happen now.
Photos by Nancy Villere – CrushPhotoStudios.com